Open AccessZEB 1‐mediated vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer
Author(s) -
Wang Hua,
Huang Bin,
Li Bai Mou,
Cao Kai Yuan,
Mo Chen Qiang,
Jiang Shuang Jian,
Pan Jin Cheng,
Wang Zong Ren,
Lin Huan Yi,
Wang Dao Hu,
Qiu Shao Peng
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13637
Subject(s) - vasculogenic mimicry , prostate cancer , epithelial–mesenchymal transition , cancer research , vimentin , cancer stem cell , biology , gene knockdown , homeobox protein nanog , prostate , cancer , stem cell , pathology , metastasis , immunohistochemistry , microbiology and biotechnology , immunology , medicine , cell culture , embryonic stem cell , biochemistry , genetics , induced pluripotent stem cell , gene
The zinc finger E‐box‐binding homeobox 1 ( ZEB 1) induced the epithelial–mesenchymal transition ( EMT ) and altered ZEB 1 expression could lead to aggressive and cancer stem cell ( CSC ) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD 34/periodic acid–Schiff double staining. Prostate cancer cells were subjected to ZEB 1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB 1‐induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB 1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD 133 in prostate cancer tissues. Furthermore, ZEB 1 was required for VM formation and altered expression of EMT ‐related and CSC ‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB 1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB 1 in prostate cancer cells were mediated by Src signalling; that is PP 2, a specific inhibitor of the Src signalling, dose dependently reduced the p‐Src 527 level but not p‐Src 416 level, while ZEB 1 knockdown also down‐regulated the level of p‐Src 527 in PC 3 and DU ‐145 cells. PP 2 treatment also significantly reduced the expression of VE ‐cadherin, vimentin and CD 133 in these prostate cancer cells. Src signalling mediated the effects of ZEB 1 on VM formation and gene expression.